Mesenchymal stem cells transplantation ameliorates glomerular injury in streptozotocin-induced diabetic nephropathy in rats via inhibiting macrophage infiltration

Lv, Shunzeng; Liu, Gang; Wang, Jianping; Wang, Weiwei; Cheng, Jing; Sun, Aili; Liu, Haiying; Nie, Huibin; Su, Moran; Guan, Guangju

doi:10.1016/j.intimp.2013.05.031

Cited by 75 publications

(70 citation statements)

References 58 publications

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“…[11][12][13][14] Because infusion of autologous mesenchymal stem cells (MSCs) is considered to be safe and has few adverse effects, it also seems to be promising for clinical use. In preliminary experiments, 15 we found that MSCs injected via the tail vein into rats with DN reduced blood glucose, microalbuminuria and ameliorated glomerular injury; however, the gross presence of stem cells was not found in the kidney, which was also demonstrated by other studies. [16][17][18] So, we speculated that MSCs protected the kidney via paracrine action.…”

Section: Mesenchymal Stem Cells Ameliorate Diabetic Glomerular Fibrossupporting

confidence: 64%

“…As we have discussed in our previous article, 15 the diabetes model with a single intraperitoneal injection of STZ we chose in this study is well documented to produce hyperglycaemia and insulinitis similar to their human counterparts. 25 At 8 weeks after STZ injection, diabetes rats develop severe hyperglycaemia, albuminuria, enhanced Ccr and glomerular pathological changes, all of which are characteristics of early stage of DN.…”

Section: Discussionmentioning

confidence: 99%

“…In our previous study, 15 MSCs were transducted with lentiviral-transduced green fluorescent protein as a cell tracker to assess the intrarenal localization of MSCs. We found that at 24 h after transplantation, a small amount of MSCs was present around the glomeruli and near vessels in kidney of MSC-treated diabetic rats, but at 8 weeks after transplantation, there was only few MSCs found in glomeruli and not found elsewhere, at which time the protective effect of stem cells on diabetic kidney still existed.…”

Section: Discussionmentioning

confidence: 99%

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Mesenchymal stem cells ameliorate diabetic glomerular fibrosis in vivo and in vitro by inhibiting TGF-β signalling via secretion of bone morphogenetic protein 7

Liu

Sun

et al. 2014

Diabetes and Vascular Disease Research

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Purpose: To investigate whether mesenchymal stem cells (MSCs) could inhibit transforming growth factor beta (TGF-β) signalling pathway by paracrine action. Methods: Bone marrow-derived MSCs were transplanted to streptozotocin-induced diabetic rats via tail vein. MSCconditioned media were used with a model of mesangial cell fibrosis induced by high glucose in vitro. Results: At 8 weeks after MSC treatment, the renal function and the glomerulosclerosis as revealed by periodic acid Schiff stain was dramatically attenuated. The expression of collagen I, collagen IV and α-smooth muscle actin (SMA) in diabetic kidney was decreased, and E-cadherin increased after MSC treatment. The TGF-β signalling pathway was suppressed both in vivo and in vitro. MSCs secreted a significant amount of bone morphogenetic protein 7 (BMP7), in vitro, MSC-conditioned media inhibited TGF-β signalling stimulated by high glucose, and BMP7 neutralizing antibody blocked the inhibitory effect of MSC-conditioned media. Conclusion: MSCs ameliorated glomerular fibrosis in vivo and in vitro by inhibiting TGF-β/Smad signalling pathway via secretion of BMP7.

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Section: Mesenchymal Stem Cells Ameliorate Diabetic Glomerular Fibrossupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Mesenchymal stem cells ameliorate diabetic glomerular fibrosis in vivo and in vitro by inhibiting TGF-β signalling via secretion of bone morphogenetic protein 7

Liu

Sun

et al. 2014

Diabetes and Vascular Disease Research

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“…Modification of the expression of immunomodulators has also been proposed as a possible mechanism for the renoprotective effects of MSCs. In a rodent model of DM and diabetic nephropathy, MSC treatment ameliorated diabetic nephropathy via inhibition of MCP-1 expression by secreting HCP, thus reducing macrophage infiltration and down-regulating Il-1β, IL-6, and TNF-α expression in the renal tissue of diabetic rates (116). Others have found beneficial effects of a targeted treatment of MSC administration, using an ultrasound-targeted microbubble destruction (UTMD) technique.…”

Section: Msc-based Therapies For Diabetic Microvascular Complicationsmentioning

confidence: 99%

Mesenchymal Stem Cell-Based Treatment for Microvascular and Secondary Complications of Diabetes Mellitus

et al. 2014

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The worldwide increase in the prevalence of Diabetes mellitus (DM) has highlighted the need for increased research efforts into treatment options for both the disease itself and its associated complications. In recent years, mesenchymal stromal cells (MSCs) have been highlighted as a new emerging regenerative therapy due to their multipotency but also due to their paracrine secretion of angiogenic factors, cytokines, and immunomodulatory substances. This review focuses on the potential use of MSCs as a regenerative medicine in microvascular and secondary complications of DM and will discuss the challenges and future prospects of MSCs as a regenerative therapy in this field. MSCs are believed to have an important role in tissue repair. Evidence in recent years has demonstrated that MSCs have potent immunomodulatory functions resulting in active suppression of various components of the host immune response. MSCs may also have glucose lowering properties providing another attractive and unique feature of this therapeutic approach. Through a combination of the above characteristics, MSCs have been shown to exert beneficial effects in pre-clinical models of diabetic complications prompting initial clinical studies in diabetic wound healing and nephropathy. Challenges that remain in the clinical translation of MSC therapy include issues of MSC heterogeneity, optimal mode of cell delivery, homing of these cells to tissues of interest with high efficiency, clinically meaningful engraftment, and challenges with cell manufacture. An issue of added importance is whether an autologous or allogeneic approach will be used. In summary, MSC administration has significant potential in the treatment of diabetic microvascular and secondary complications but challenges remain in terms of engraftment, persistence, tissue targeting, and cell manufacture

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“…Количество дан-ных клеток увеличивается по мере развития гломеруляр-ного и интерстициального фиброза [3][4][5][6]. Накапливается все больше данных о том, что воспалительные реакции c участием макрофагов играют важную роль в прогрессиро-вании ДН [6][7][8][9]. Воспалительные медиаторы -молекулы адгезии (ICAM-1, VCAM-1), интерлейкин-6 (IL-6) явля-ются биомаркерами прогрессирования нефропатии у больных СД-2 [10,11].…”

Section: терапевтический архив 6 2015unclassified

Increased serum concentrations of inflammatory cytokines in type 2 diabetic patients with chronic kidney disease

Климонтов²,

Myakina³

et al. 2015

Ter. arkh.

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Mesenchymal stem cells transplantation ameliorates glomerular injury in streptozotocin-induced diabetic nephropathy in rats via inhibiting macrophage infiltration

Cited by 75 publications

References 58 publications

Mesenchymal stem cells ameliorate diabetic glomerular fibrosis in vivo and in vitro by inhibiting TGF-β signalling via secretion of bone morphogenetic protein 7

Mesenchymal stem cells ameliorate diabetic glomerular fibrosis in vivo and in vitro by inhibiting TGF-β signalling via secretion of bone morphogenetic protein 7

Mesenchymal Stem Cell-Based Treatment for Microvascular and Secondary Complications of Diabetes Mellitus

Increased serum concentrations of inflammatory cytokines in type 2 diabetic patients with chronic kidney disease

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